Abstract
[Introduction] Quorum Sensing has recently been recognized as a type of signal transduction that senses the cell-population density and responds to changes in the cell number between bacteria cells. Its mechanism is controlled by the hormone-like low molecular autoinducer (AI). There have been numerous investigations of the regulation of bacterial using AI inhibitors, and synthetic analogs. On the other hand, little is known regarding the effects of AI inhibitors on the growth of human cells. The present study, examined the possibility of 96 synthetic autoinducer analogs of Pseudomonas aeruginosa quorum sensing having both suppressive and radiosensitizing effects on the growth of human oral cavity carcinoma cells.
[Materials and Methods] Synthetic 96 AI analogs of Pseudomonas aeruginosa quorum sensing were provided by Otsuka Chemical. The suppressive and radiosensitizing effects were tested by using human oral cavity carcinoma cell lines derived from tongue cancer cells (SAS) and gingival carcinoma cells (Ca9-22). Each cell line was cultured in liquid culture media containing 10 % fetal bovine serum. The clonogenic potential was tested by the plasma clot technique using platelet-poor human plasma. X irradiation was administered with an X-ray generator using 150 kV, 20 mA, 0.5-mm aluminum plus 0.3-mm copper filters at a dose of 90—100 cGy/min.
[Results and Discussion] A couple of compounds showed a significant suppressive effect on the growth of the SAS and Ca9-22 cell lines. The IC50 (50 % inhibition concentration) was in the range of 1.5—3.5 μg/ml in SAS and 2.2—5.4 μg/ml in Ca9-22. The radiosensitizing effect was observed with a 1 μg/ml compound and 2 Gy irradiation. These results demonstrated that some AI analogs showed anti-proliferative activity in human tumor cell lines. Currently, more detailed studies are underway to elucidate the structure activity relationships and suppressive mechanisms.
